STAT1-caspase 3 pathway in the apoptotic process associated with steroid-induced necrosis of the femoral head

• Published in: Journal of molecular histology 2014-08, Vol.45 (4), p.473-485
• Main Authors: Xu, Xinxian, Wen, Hong, Hu, Yuezheng, Yu, Huachen, Zhang, Yu, Chen, Chengwang, Pan, Xiaoyun
• Format: Article
• Language: English
• Subjects: Adult; Apoptosis - genetics; Apoptosis - physiology; Biomedical and Life Sciences; Biomedicine; Caspase 3 - genetics; Caspase 3 - metabolism; Cell Biology; Developmental Biology; Female; Femur Head Necrosis - chemically induced; Femur Head Necrosis - metabolism; Humans; Life Sciences; Male; Middle Aged; Original Paper; STAT1 Transcription Factor - genetics; STAT1 Transcription Factor - metabolism; Steroids - toxicity
• ISSN: 1567-2379; 1567-2387
• DOI: 10.1007/s10735-014-9571-6

Osteocyte apoptosis is the main manifestation of steroid-induced avascular necrosis of the femoral head (SANFH). STAT1 and caspase 3 participate in the process of apoptosis and STAT1 upregulates the expression of caspase 3. We examined the relationship between the STAT1-caspase 3 pathway and apoptosis in SANFH. All specimens were divided into four groups: the negative control group, Ficat I–II group, Ficat III group, and Ficat IV–V group, and examined histologically, with a TUNEL assay, immunohistochemically, with a caspase 3 activity assay, with ELISAs of STAT1 and phospo-STAT1 (p-STAT1), with a western blotting analysis of p-STAT1 and with real-time RT-PCR. The proportion of empty lacunae increased significantly with the development of SANFH. The proportion of TUNEL-positive cells and immunohistochemical analysis of caspase 3 also increased significantly, although the Ficat I–II group did not differ significantly from the negative control group. Immunohistochemical analysis of STAT1 and p-STAT1, caspase 3 activity all showed significant differences among the groups. An ELISA and a western blotting analysis of p-STAT1 showed significant differences among the groups. An ELISA of STAT1, real-time RT-PCR analysis of caspase 3 and STAT1 all showed significant differences among the groups except between the Ficat I–II and negative control groups. The correlation analysis showed strong positive relationships between the proportion of empty lacunae and the proportion of TUNEL-positive cells between caspase 3 activity and the proportion of TUNEL-positive cells and between the levels of p-STAT1 protein and caspase 3 mRNA. The apoptotic process in SANFH develops with the upregulated expression of caspase 3 via the expression and activation of STAT1. The STATI-caspase 3 pathway plays a critical role in the development of SANFH.